No means exist to prevent, arrest, or reverse the relentless and progressive renal failure that clincally characterizes adult polycystic kidney disease (APKD), an entity that contributes significantly to patient numbers and programmatic costs in the federally sponsored endstage renal disease program. A Program Project has been designed to identify avenues by which the control of renal failure in APKD might be achieved. Eight institutions will be involved in the conduct of ten projects. They will employ biochemical, microscopical, microbiological, medical, and surgical techniques in the study of the structure and function of kidneys from the CFWw mouse (a model of heritable renal cystic disease) and the CD rat fed cystogenic chemicals (a model of acquired renal cystic disease), and from affected humans, whose kidneys become available at times of organ donation or autopsy. The projects will address six questions concerning renal cystic disease, spanning the lesion from predisposed to endstage kidney: In the predisposed kidney are nephrons normal? Why do cysts form? Do cysts function? why do cysts grow? Does cyst growth cause renal failure? Can function in the endstage kidney be improved? Specific topics of investigation include the composition, metabolism, and compliance of renal tubular basement membrane; the growth of renal tubular epithelium; the patency of cystic nephrons; host-microbe interaction in cyst development; the penetration of cysts by antimicrobials; and the impacts of enlargement and reduction in cyst size on overall renal function. The Project will be supported by three cores: Administration Mouse Colony, and Organ Procurement. The results of this program will identify which of the following goals must be established if the renal failure of APKD is to be successfully controlled: correction of the enzymatic defect that leads to faulty basement membrane production, control of the epithelial proliferation that partially obstructs nephrons, control of the growth of cysts that compress and destroy normal adjacent kidney, or control of microbes that cause cysts to form or expand.